Plasma Β-endorphin Levels Research Articles

The relationship of plasmaβ-endorphins and pain dimensions in primary liver cancer patients using the Chinese Cancer Pain Assessment Tool

Evidence suggests a mind-body link in pain experience. Many studies have focused on the link between endorphins and pain intensity. However, there is a lack of research that examines the bio-psycho-socio-cultural link from a multidimensional perspective in cancer pain experience. Methods: This cross-sectional correlational study investigated the relationship between plasma β-endorphin level (objective variable) and the pain dimensions (subjective variables). Venous blood samples were taken from 76 Chinese primary liver cancer patients by convenience in a cancer centre and plasma β-endorphin levels were measured by radioimmunoassay. The Chinese Cancer Pain Assessment Tool (CCPAT) was employed to assess the pain dimensions which include: functional, psychosocial, pharmacological, emotional, pain beliefs and meanings, pain intensity. Results and Discussion: Sixty-eight men and eight women were recruited the mean age was 49.8 (±12.2) years. Thirty-two (42.1%) patients experienced varying degrees of pain. The mean β-endorphin level was 270.4 (± SEM 11.4)pg/ml. The mean weighted CCPAT scores were 27.8 (±8.9), 14.6 (±2.1), 19.0 (±4.1), 23.1 (±6.4), 70.1 (±8.3) and 0.8 (±1.5) for functional, psychosocial, pharmacological, emotional, pain beliefs and meanings, pain intensity dimensions respectively. Spearman's correlations demonstrated a significant relationship between β-endorphin level and the psychosocial dimension scores (r = −0.25, p = 0.028) in the pain and control groups. Inverse correlations between plasma β-endorphin level and all CCPAT pain dimension scores were found. The results are consistent with those of a previous study by Chung et al. in 2002. Conclusions: Our study suggests that there is a mind-body link in cancer pain experience. Establishment of this link will enhance more accurate pain assessment and provide a basis for multidisciplinary pain interventions, fostering better pain management.

Common traditional Chinese medicinal herbs for dysmenorrhea

Dysmenorrhea is painful menstrual cramps, which negatively impacts the quality of life of those diagnosed. The paper reviews traditional Chinese medicine's treatment of dysmenorrhea through the use of combination-herbal-formula therapeutics. These herbal treatments are effective for dysmenorrhea with minimal side effects. Pharmacological studies suggest Chinese herbal dysmenorrhea therapies likely decrease prostaglandin levels, modulate nitric oxide, increase plasma beta-endorphin (beta-EP) levels, block calcium-channels and improve microcirculation. Conventional therapy for dysmenorrhea, which usually includes non-steroidal antiinflammatory drugs (NSAIDs), provides symptomatic relief but has increasing adverse effects with long-term use. Therefore, Chinese herbal medicines, including simple herbal and combination formulas, are perhaps the ideal therapeutics of choice.

Relationship between plasma β -Endorphin level and the Cerebral CT Value in Neonatal Asphyxia

目的 研究窒息新生儿血浆β-内啡肽(β-EP)的含量,探讨它与新生儿窒息及窒息后脑损伤的关系.方法采用放射免疫分析法测定37例窒息新生儿及12例健康新生儿血浆β-EP含量,同时行头颅CT检查,并测定脑实质CT值.结果窒息组血浆β-EP含量明显高于对照组,重度窒息组β-EP明显高于轻度窒息组,差异均有显著意义.CT值比较结果示:窒息组CT值明显低于对照组,重度窒息组明显低于轻度窒息组,差异均有显著意义;轻、重度窒息组血浆β-EP水平与脑实质CT值呈显著负相关(γ分别为0.696、0.809,P＜0.01),但对照组血浆β-EP水平与脑实质CT值相关分析,无统计学意义.结论血浆β-EP含量及CT值与窒息程度密切相关,窒息越重,血浆β-EP含量越高,CT值越低.血浆β-EP可作为观察新生儿窒息程度和窒息后脑损伤的指标。

Plasma β-endorphin levels in frequent and infrequent tanners before and after ultraviolet and non-ultraviolet stimuli

To the Editor: Ultraviolet (UV) exposure behavior exhibits similarities to other substance-related disorders.1Warthan M.M. Uchida T. Wagner Jr., R.F. UV light tanning as a type of substance-related disorder.Arch Dermatol. 2005; 141: 963-966Crossref PubMed Scopus (128) Google Scholar UV exposure has a direct reinforcing effect on frequent tanners.2Feldman S.R. Liguori A. Kucenic M. Rapp S.R. Fleischer Jr., A.B. Lang W. et al.Ultraviolet exposure is a reinforcing stimulus in frequent indoor tanners.J Am Acad Dermatol. 2004; 51: 45-51Abstract Full Text Full Text PDF PubMed Scopus (118) Google Scholar Cutaneous opioids are induced by UV exposure,3Wintzen M. Yaar M. Burbach J.P. Gilchrest B.A. Proopiomelanocortin gene product regulation in keratinocytes.J Invest Dermatol. 1996; 106: 673-678Crossref PubMed Scopus (128) Google Scholar but whether the reinforcement seen with UV exposure is caused by opioid release is unknown. The potential relationship is complicated, as larger studies have not found an effect of UV on plasma β-endorphin levels.4Wintzen M. Ostijn D.M. Polderman M.C. le Cessie S. Burbach J.P. Vermeer B.J. Total body exposure to ultraviolet radiation does not influence plasma levels of immunoreactive beta-endorphin in man.Photodermatol Photoimmunol Photomed. 2001; 17: 256-260Crossref PubMed Scopus (36) Google Scholar These conflicting results could be caused by differences in UV dose and subject populations, because the tests were not done under conditions in which preference for the UV stimulus was known to occur. To better understand the relationship between cutaneous opioids and the reinforcing effect of UV exposure, we conducted a small double-blind, placebo-controlled, randomized trial and assessed plasma β-endorphin levels in 3 frequent and 3 infrequent adult female tanners, between 25 and 32 years of age and skin types III and IV, before and after non-UV and UV exposures (10 min for frequent tanners and 5-9 min for infrequent tanners based on minimal erythema dose testing). The study was approved by the Institutional Review Board (IRB). Infrequent tanners were defined as individuals who had tanned intermittently in the past (fewer than 8 times per year) but who are not regular tanners. Frequent tanners were defined as tanners who tan more often than is necessary to maintain a tan (8-15 times per month). Commercial indoor tanning beds with Speed 175 and 205 bulbs were used. The bulbs have a UV output of 4% in the UVB range and 96% in the UVA range (estimate dosage of 22.4 j/cm2). Plasma β-endorphin levels were measured on the same day by enzyme-linked immunosorbent assay (MD Biosciences Inc, St Paul, Minn) from blood samples drawn 3 times: before exposure, immediately after non-UV bed, and immediately after UV bed. No discernable trend in plasma β-endorphin levels was observed among the 6 subjects (Fig 1), though the mean plasma β-endorphin level was slightly higher in frequent tanners exposed to UV as compared to baseline. Baseline β-endorphin levels vary and exhibit no distinct pattern of response to UV exposure (at one exposure time in these 6 subjects). The variability in plasma β-endorphin levels complicates attempts to understand the role of endorphins in mediating the preference for UV. Even anxiety about the blood draw could affect endorphin levels. Opioid inhibitor studies may be a better approach to characterize the role of endorphin related effects in mediating physiologic responses to UV.

There is a gender difference in the relationship between metabolic syndrome and oxidative stress among Japanese

Neurobiological mechanisms invoking the release of endogenous opioids and depression of stress hormone release are believed to be the basis of acupuncture analgesia. This study compared plasma β-endorphin and cortisol levels with self assessment scores of intensity of pain, before and after 10 days of electro-acupuncture treatment in patients suffering from chronic pain as a result of osteoarthritis knees. Forty patients of either sex over 40 years with primary osteoarthritis knee were recruited into a single-blinded, sham-controlled study. For electro-acupuncture group the points were selected according to the Traditional Chinese Medicine Meridian Theory. In the sham group needles were inserted at random points away from true acupoints and no current was passed. Both groups were treated for 10 days with one session every day lasting for 20–25 min. Pre- and post-treatment Western Ontario and McMaster Universities (WOMAC) index of osteoarthritis knee and Visual Analogue Scale (VAS) for pain were recorded and blood samples were taken for the measurement of plasma cortisol and β-endorphin levels. Following electro-acupuncture treatment there was a significant improvement in WOMAC index and VAS (p = 0.001), a significant rise in plasma β-endorphin (p = 0.001), and a significant fall in plasma cortisol (p = 0.016). In conclusion electro-acupuncture resulted in an improvement in pain, stiffness and disability. Of clinical importance is that an improvement in objective measures of pain and stress/pain associated biomarkers was shown above that of a sham treatment; hence demonstrating acupuncture associated physiological changes beyond that of the placebo effects.

Differences in the Peripheral Levels of ??-endorphin in Response to Alcohol and Stress as a Function of Alcohol Dependence and Family History of Alcoholism

Evidence indicates that both genetic and environmental factors, such as stress, may play an important role for the development of alcoholism, while beta-endorphin may be implicated in the control of alcohol consumption. The objective of the present studies was to test the hypothesis that there are differences in the response of the pituitary beta-endorphin system to stress as a function of family history of alcoholism and alcohol dependence. The response of the pituitary beta-endorphin to a placebo or an alcohol (0.50 g ethanol/kg) drink and to a stress task performed 30 min following ingestion of either the placebo or the alcohol drink was measured in social and heavy drinkers with [high risk (HR)] and without [low risk (LR)] a family history of alcoholism. Thus, each subject participated in 4 experimental sessions given on different days in a randomized order. Four groups of subjects were investigated: 1) low risk nonalcoholics (LRNA); 2) high risk nonalcoholics (HRNA), 3) low risk alcoholics (LRA); and 4) high risk alcoholics (HRA). Plasma beta-endorphin was estimated prior to and for 3.5 hr post-stress. Changes in the concentration of plasma beta-endorphin following ingestion of either the placebo or alcohol drink without performance of the stress task served as controls to compare the stress-induced changes. Basal plasma beta-endorphin levels were higher in LRNA than LRA, HRNA and HRA participants, while basal plasma beta-endorphin levels were higher in LRA than those in HRNA and HRA participants. Furthermore, there was no significant difference in the plasma beta-endorphin levels between HRNA and HRA participants. Stress, induced a significant increase in plasma beta-endorphin concentration in all four groups of participants. However, the stress-induced increase in plasma beta-endorphin levels was more pronounced in LRNA than HRNA, LRA and HRA participants. Thus, alcohol dependence decreased the basal plasma beta-endorphin levels in LR only, as well as the stress induced increase in plasma beta-endorphin levels of participants without, but not of those with, a family history of alcoholism. Alcohol prior to stress attenuated the stress-induced increase in plasma beta-endorphin levels of all four groups of participants. The present data indicates that there are differences in both, the basal plasma beta-endorphin levels as well as the response of the pituitary beta-endorphin to stress as a function of family history of alcoholism and alcohol dependence. Thus, in HR individuals a dysfunction in the activity of the pituitary beta-endorphin system predates the development of alcoholism, while in LR individuals it develops following alcohol dependence. Furthermore, alcohol dependence did not alter the alcohol-induced attenuation of beta-endorphin response to stress.

Changes in the beta-endorphin plasma level after repeated treatment with acamprosate in rats selectively bred for high and low alcohol preference

The aim of this study was to evaluate the beta-endorphin (β-endorphin) plasma level in Warsaw Low Preferring (WLP) and Warsaw high-preferring (WHP) rats after repeated administration of acamprosate, one of most effective drug in the treatment of alcoholism. Treatment with acamprosate in dose 200 mg/kg, p.o. for 10 days induced an increase in plasma β-endorphin levels. A single injection of ethanol also results in the increase of β-endorphin level. Moreover, it was found that single injection of ethanol to WHP rats resulted in lower increase of plasma β-endorphin content in rats earlier treated with acamprosate. In WLP rats, repeated acamprosate treatment prevents the ethanol-induced increase in plasma β-endorphin level. It may be concluded that acamprosate modulates the endogenous opioid system.

Multi-factor analysis of umbilical plasma β-endorphin levels in neonates

目的 研究不同妊娠、分娩因素对脐血β内啡肽(β-EP)水平的影响.方法收集不同孕期的新生儿脐血共95例,用放射免疫法测定其β-EP水平,以β-EP为因变量,以新生儿胎龄、性别、出生体重、分娩方式、母患高血压、母患糖尿病、宫内窘迫、胎膜早破为自变量,进行多元线性逐步回归,筛选出可能的影响因素,进一步研究不同影响因素时脐血β-EP变化.结果胎龄、分娩方式、宫内窘迫是影响脐血β-EP水平的重要因素(P均＜0.05).早产儿组脐血β-EP值高于足月儿组,分别为(409.5±150.1)pg/ml、(261.4±141.5)pg/ml,差异均有统计学意义(P均＜0.05).阴道分娩组及产钳助产组高于选择性剖宫产组,差异有统计学意义(P均＜0.05).阴道分娩组与产钳助产组比较,差异无统计学意义(P均＞0.05).宫内窘迫组高于无宫内窘迫组,差异有统计学意义(P均＜0.01).结论分娩应激、疼痛会使β-EP升高,缺氧是影响β-EP水平的一个重要因素,脐血β-EP水平可作为胎儿缺氧的一个指标.早产儿脐血β-EP高于足月儿是否是早产儿易发生呼吸暂停的病理生理基础,有待进一步研究。

Involvement of serotonin in the hypoglycemic response to 2 Hz electroacupuncture of zusanli acupoint (ST36) in rats

In our previous studies, an insulin-dependent hypoglycemic effect produced by electroacupuncture (EA) was shown to be mediated by endogenous opioid peptides (EOP). In the present study, we applied 2 Hz EA to both zusanli acupoints (ST36) in the test group for 30 min, and to a nonacupoint area in the control group for 30 min to compare the acupoint specific character in the hypoglycemic effect of EA. Assays of plasma β-endorphin and insulin levels were performed by ELISA kits. The insulin-dependent mechanism of the hypoglycemic effect was also investigated in streptozotocin (STZ)-induced diabetic rats. The mediation of EOP and the role of μ-opioid receptor were examined by naloxone and μ-opioid receptor knockout mice (MOR-KOM). The serotonin depletion was carried out by injecting (i.p.) p-chlorophenylalanine (PCPA); two low doses of serotonin were also injected (i.v.) to analyze the direct effect on plasma glucose levels. The hypoglycemic effect of EA was much greater in rats stimulated at ST36 than in rats receiving the same stimulation at the nonacupoint area. The plasma levels of insulin and β-endorphin were also significantly elevated after stimulation of both zusanli acupoints, but remained unchanged following stimulation at the nonacupoint area. There was no sharp hypoglycemic response to 2 Hz EA at zusanli acupoint of STZ-induced diabetic rats. However, the hypoglycemic effect of this EA was not totally blocked by the sufficient dose of naloxone (1 mg/kg, i.v.). Additionally, 2 Hz EA at ST36 also showed a sharp decrease in plasma glucose levels of MOR-KOM. Pretreatment with PCPA did not reproduce hypoglycemic response to 2 Hz EA in naloxone-treated rats and MOR-KOM mice. Furthermore, injection of serotonin decreased the plasma glucose levels significantly. Therefore, we suggest that serotonin also involved in the hypoglycemic action of 2 Hz EA at both zusanli acupoints of normal rats.

Multiple sources of endogenous opioid peptide involved in the hypoglycemic response to 15 Hz electroacupuncture at the Zhongwan acupoint in rats

A decrease in plasma glucose levels was observed in rats which received electroacupuncture (EA) stimulation at the Zhongwan acupoint. In the present study, the role of the adrenal gland in this hypoglycemic response to EA at high frequency (15 Hz) was investigated on adrenalectomized (ADX) normal rats. There was a sharper decrease in plasma glucose by EA stimulation in the fasting ADX group than in the fasting sham-operated group. Naloxone blocked this hypoglycemic response to EA stimulation in rats which received ADX. Stimulation of EA failed to elicit an increase in plasma β-endorphin and insulin levels in ADX rats. Similar results were observed in sham and ADX mice. EA stimulation of ADX mice can reduce plasma glucose levels. Furthermore, naloxone abolished the hypoglycemic response to EA stimulation in mice. Such a hypoglycemic response to EA stimulation was also observed in μ-opioid receptor knockout mice (MOR-KOM). Mediation by another opioid peptide should also be considered in future experiments. We conclude that multiple sources of endogenous opioid peptide participated in the lowering of plasma glucose in rats induced by EA stimulation at higher frequency (15 Hz) at the Zhongwan acupoint. Increase in β-endorphin levels from the adrenal gland enhances the secretion of insulin, there by reducing plasma glucose levels, and is partially involved in this EA stimulation.

Raloxifene treatment increases plasma levels of β-endorphin in postmenopausal women: a randomized, placebo-controlled study

Objective: To evaluate the effect of the selective estrogen receptor modulator raloxifene hydrochloride (Evista, Eli Lilly and Company, Indianapolis, IN) on plasma levels of β-endorphin, and to determine whether β-endorphin levels and menopausal symptoms are related. Design: A randomized, double-blind, placebo-controlled pilot study. Setting: Endocrinology outpatient department. Patient(s): Forty postmenopausal women. Intervention(s): The women received raloxifene, 60 mg/d, or placebo for 3 months. A questionnaire on climacteric symptoms was administered before and after treatment. Main Outcome Measure(s): Circulating levels of β-endorphin, climacteric symptom score, and correlation with β-endorphin levels. Result(s): Raloxifene treatment significantly increased levels of β-endorphin and did not significantly affect climacteric symptoms, with the exception of worsening vasomotor symptoms. No significant relation was seen between plasma levels of β-endorphin and climacteric symptoms. Conclusion(s): Raloxifene modulates plasma levels of β-endorphin without concomitantly relieving climacteric symptoms, as seen with hormone replacement therapy.

Alcohol urge and plasma β-endorphin change after alcohol challenge with naltrexone pretreatment in social drinkers

The authors have investigated the effect of naltrexone (NTX) on lowering the urge of alcohol drinking and the action mechanism of NTX. Fifteen healthy male social drinkers voluntarily participated. The experimental method was a double-blind, placebo-controlled cross-over design. To eliminate NTX effect, 1 week washout cross-over interval was taken. Subjects ingested NTX, 50 mg/day, or placebo for 1 week. Then, the alcohol (0.5 ml/kg) challenge test was done in the evening. Blood samples were taken immediately before drinking, at 20 min and at 60 min after alcohol drinking. Plasma β-endorphin, plasma ACTH and serum cortisol levels were checked. Subjects completed self-report questionnaires such as the visual analog scales of drink urge and the alcohol sensation scales at regular intervals. In the case of NTX pretreatment, the subjects reported significantly ( P=.013) less urge to drink alcohol on the self-reporting urge scales, especially at postdrinking 20 min and 60 min than placebo pretreatment. After alcohol challenge, the subjects reported significantly more dizziness ( P=.015) in the case of NTX pretreatment, and reported less mood elevation trend, though not significant ( P=.052). Basal plasma β-endorphin levels were not different, but in the case of NTX pretreatment, the increasing degree of plasma β-endorphin during 20 min after alcohol challenge was significantly ( P=.039) higher than with placebo pretreatment. This results show that the NTX reduced the urge to drink alcohol with the mechanism of partially blocking the opioid positive reward system and partially mimicking the alcohol effect.

Analgesic effect of calcitonin in osteoporosis

Bone pain is the most common symptom in osteoporotic patients. To date, there is mounting evidence that calcitonin significantly reduces bone pain in osteoporosis, and that the analgesic effect can be evident as soon as the second week of treatment. The limitations to the use of calcitonin, which are parenteral administration and side effects, can now be overcome by the availability of the nasal spray preparation. At present, controlled studies have demonstrated the analgesic activity of calcitonin given by nasal spray in patients with vertebral crush fractures and bone pain. The mechanism for the analgesic effect of calcitonin is yet to be clarified. In humans, similarities between calcitonin and morphine-induced analgesia, and reports of calcitonin-induced elevation of plasma β-endorphin levels, suggest the possible involvement of the endogenous opiate system in mediating the analgesic action of calcitonin. However, the demonstration of calcitonin binding sites in areas of the brain involved in pain perception and a series of animal studies have raised the possibility that calcitonin may directly modulate nociception in the central nervous system. In support of this hypothesis are some observations of an analgesic effect obtained by direct epidural or subaracnoidal injection of calcitonin in humans.

Naloxone cannot abolish the lack of oxytocin release during unexperienced suckling of dairy cows

To evaluate the role of opioids for the regulation of oxytocin release in response to teat stimulation, 10 brown-Swiss dairy cows were randomized to two experiments during mid of lactation. In the first experiment, four cows without previous suckling experience were suckled by an alien calf between two normal milkings. Before and during milking or suckling, frequent blood samples were collected via a jugular cannula for determination of oxytocin and β-endorphin. In the second experiment, six cows were treated with naloxone or saline, 10 min before the start of the first or second suckling, respectively. The collected blood samples were assayed for oxytocin. In the first experiment, the plasma levels of β-endorphin were elevated during and after the unexperienced suckling in three cows, but not in the fourth cow, and the release of oxytocin during suckling was markedly reduced, suggesting no release of alveolar milk. In the second experiment, the release of oxytocin during suckling was again significantly reduced. Pretreatment with naloxone before suckling did not completely abolish the adverse effect of suckling and the oxytocin plasma level did not increase to levels comparable with control milking. In emotional stress situations, the release of oxytocin from the pituitary is inhibited with simultaneously elevated β-endorphin plasma levels. Although there is some evidence for a regulatory role of opioids for the release of oxytocin, other mediators are suggested to be more potent in regulating oxytocin under stress conditions.

Plasma β-endorphin levels in obese and non-obese patients with polycystic ovary disease

The aim of this study was to determine the influence of body weight on circulating plasma levels of β-endorphin and insulin in women with polycystic ovary disease (PCOD) ,as well as the correlation between the plasma levels of β-endorphin and insulin. One-hundred and sixty-seven consecutive subjects with PCOD were recruited ,117 of whom had normal weight (body mass index (BMI) < 25) while 50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of β-endorphin ,insulin ,gonadotropins ,prolactin ,progesterone ,17β-estradiol ,estrone ,androgens ,dehydroepiandrosterone sulfate and sex hormone-binding globulin (SHBG) were measured. Mean β-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones. Correlation analysis showed a positive association between insulin and β-endorphin ,β-endorphin and BMI (and weight) ,insulin and BMI (and weight) ,and a negative correlation was found between insulin and SHBG. A weak association was found between-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma-endorphin concentrations correlate more with BMI than with insulinemia.

Plasma β-endorphin levels in obese and non-obese patients with polycystic ovary disease

The aim of this study was to determine the influence of body weight on circulating plasma levels of β-endorphin and insulin in women with polycystic ovary disease (PCOD) ,as well as the correlationbetween the plasma levels of β-endorphin and insulin.One-hundred and sixty-seven consecutive subjects with PCOD were recruited ,117 of whom had normal weight (body mass index (BMI) < 25) while50 were obese (BMI > 25). A venous blood sample was taken and plasma concentrations of β-endorphin ,insulin ,gonadotropins ,prolactin ,progesterone ,17β-estradiol ,estrone ,androgens ,dehydroepiandrosteronesulfate and sex hormone-binding globulin (SHBG) were measured.Mean β-endorphin and insulin plasma levels were significantly higher (p < 0.05) in obese PCOD women than in non-obese ones.Correlation analysis showed a positive association between insulin and β-endorphin ,β-endorphin and BMI (and weight) ,insulin and BMI (and weight) ,and a negative correlation was found betweeninsulin and SHBG. A weak association was found between-endorphin and luteinizing hormone (LH) in peripheral plasma. Stratified and linear regression analysis showed that plasma-endorphin concentrationscorrelate more with BMI than with insulinemia.

Neuroendocrine effects of raloxifene hydrochloride in postmenopausal women

Raloxifene is a selective estrogen modulator able to exert an estrogen-like action on some target tissues and a specific antiestrogenic action on the uterus and breast. In ovariectomized rats ,it has beenshown to stimulate the β-endorphin and allopregnanolone concentrations of the anterior and neurointermediate pituitary lobes ,the hypothalamus and the hippocampus. The present study aimed to evaluate,in 12 healthy postmenopausal women ,the effect of 60 mg/day raloxifene hydrochloride administration for 6 months on plasma β-endorphin and allopregnanolone levels ,and on the dynamic changes of bothβ-endorphin and allopregnanolone secretion after the administration of: (1) clonidine ,an α2-presynaptic adrenergic agonist; (2) naloxone ,an opioid receptor antagonist; and (3) fluoxetine,a serotonin selective reuptake inhibitor.The administration of raloxifene significantly increased both circulating β-endorphin and allopregnanolone concentrations ,at both the third and sixthmonths of treatment (p < 0.01). Clonidine ,fluoxetine and naloxone administration before therapy was not able to stimulate the release of β-endorphin ,but the response was completely restoredafter raloxifene administration. Before therapy ,clonidine and naloxone tests were accompanied by a significant rise in allopregnanolone secretion; the same changes were observed after raloxifene administration,but with significantly higher allopregnanolone concentrations at each time considered. While the fluoxetine test before therapy failed to increase the release of allopregnanolone ,the same test after 6months of raloxifene administration was characterized by a significant release of allopregnanolone at 60 and 90 minutes. The present data indicate that raloxifene has an estrogen-like effect on neuroendocrinepathways in postmenopausal women.

L-Carnitine in the treatment of painful diabetic neuropathy and its effect on plasma β-endorphin levels

Objective: We investigated the efficacy of l-carnitine (LC) in the treatment of painful diabetic neuropathy (DN) and its effects on levels of the endogenous peptide β-endorphin. Methods: The study group consisted of 7 diabetic patients with painful DN, 7 diabetic patients without DN, and 7 healthy control subjects. Blood samples were obtained from all participants for determination of basal β-endorphin levels. A 30-mg/kg intravenous bolus injection of LC was then administered. DN was diagnosed by electroneuromyography, and severity of pain was evaluated on a scale from 1 (transient, very mild pain) to 4 (severe pain). Results: Before treatment, the 7 patients with DN had pain scores of 1 (n = 1), 2 (n = 3), 3 (n = 2), and 4 (n = 1). After treatment, 3 patients had a score of 1, and 4 had a score of 2. Mean (± SD) basal β-endorphin levels were 22.6 ± 13.02 pg/mL in the 7 patients with DN, 26.01 ± 9.06 pg/mL in the 7 without DN, and 90.04 ± 29.11 pg/mL in the control group ( P < 0.05). In the patients with painful DN, β-endorphin levels at 3 hours and on day 15 were 31.97 ± 11.81 pg/mL and 28.73 ± 12.53 pg/mL, respectively. An acute rise in β-endorphin levels was noted at 3 hours ( P < 0.05), but patients' pain scores did not change correspondingly. The improvement in pain scores in patients with DN after 15 days of LC treatment was not associated with any significant change in β-endorphin levels. Conclusions: β-Endorphin levels are lower in diabetic patients than in the nondiabetic population. Treatment with LC is effective in treating painful DN, but this effect does not appear to be mediated by alterations in β-endorphin levels.

β-Endorphin plasma levels after intravenous administration of GnRH in female rats

Objective: The study investigates the effects of intravenously administered GnRH on plasma β-endorphin levels in female proestrous rats. Study design: Sixteen adult female proestrous Wistar rats, 220–250 g, were implanted with two indwelling catheters, one intracarotid and one intrajugular. Ten ng GnRH/100 μl distilled water or 100 μl saline (control) were infused in eight animals per group every 20 min from 12:30 to 14:30 h. Blood was withdrawn through the intracarotid catheter just before the initial infusion (12:30 h) and at 14:00, 15:30, 16:30 and 17:30 h for the determination of plasma β-endorphin levels. The Mann–Whitney test was used for comparison between GnRH-treated and control rats and the Wilcoxon test within each treatment group. Results: β-Endorphin levels of GnRH-treated rats were not significantly different at any sampling moment neither compared to preinfusion time nor to the corresponding controls. Conclusions: Intravenously administered GnRH was not sufficient for any possible effect on the secretion of β-endorphin from rat pituitary and further investigation is needed to demonstrate if a different experimental model would have any significant effect.

Six-month oral dehydroepiandrosterone supplementation in early and late postmenopause

The adrenal production of the Δ5-androgens, dehydroepiandrosterone (DHEA) and its sulfate ester dehydroepiandrosterone sulfate (DHEAS), declines linearly with aging. The evidence that DHEA or DHEAS administration may alleviate some of the problems related to aging has opened new perspectives for clinical research. The present study aims to investigate the effects of a 6-month DHEA supplementation in early and late postmenopausal women, with normal or overweight body mass index (BMI), on the level of circulating steroids, sex hormone binding globulin (SHBG), β-endorphin and gonadotropins, and on the adrenal gland response to dexamethasone suppression and adrenocorticotropic hormone (ACTH) stimulation.Early postmenopausal women (50–55 years) both normal weight (BMI 20–24, n = 9) and overweight (BMI 26–30, n = 9) and late postmenopausal women (60–65 years) both of normal weight and overweight, were treated with oral DHEA (50 mg/day). Circulating DHEA, DHEAS, 17-OH pregnenolone, progesterone, 17-OH progesterone, allopregnanolone, androstenedione, testosterone, dihydrotestosterone, estrone, estradiol, SHBG, Cortisol, luteinizing hormone, follicle stimulating hormone and β-endorphin levels were evaluated monthly and a Kupperman score was performed. The product/precursor ratios of adrenal steroid levels were used to assess the relative activities of the adrenal cortex enzymes. Before and after 3 and 6 months of therapy, each women underwent an ACTH stimulating test (10 μgi.v.in bolus) after dexamethasone administration (0.5 mg p.o.) to evaluate the response of Cortisol, DHEA, DHEAS, androstenedione, 17-OH pregnenolone, allopregnanolone, progesterone and 17-OH progesterone.The between-group differences observed before treatment disappeared during DHEA administration. Levels of 17-OH pregnenolone remained constant during the 6 months. Levels of DHEA, DHEAS, androstenedione, testosterone and dihydrotestosterone increased progressively from the first month of treatment. Levels of estradiol and estrone significantly increased after the first/second month of treatment. Levels of SHBG significantly decreased from the second month of treatment only in overweight late postmenopausal women, while the other groups showed constant levels. Progesterone levels remained constant in all groups, while 17-OH progesterone levels showed a slight but significant increase in all groups. Allopregnanolone and plasma β-endorphin levels increased progressively and significantly in the four groups, reaching values three times higher than baseline. Levels of Cortisol and gonadotropins progressively decreased in all groups.The product/precursor ratios of adrenal steroid levels at the sixth month were used to assess the relative activities of the adrenal cortex enzymes and were compared to those found before therapy. The 17,20-desmolase, sulfatase and/or sulfotransferase, 11,20-lyase and 5α-reductase activities significantly increased, while the 3β-hydroxysteroid-oxidoreductase activity did not vary. On thecontrary, the 11-hydroxylase and/or 21-hydroxylase activities showed a significant decrease after 6 months of treatment.In basal conditions, dexamethasone significantly suppressed all the adrenal steroids and this suppression was greater after 3 and 6 months of treatment for DHEA, DHEAS and allopregnanolone, while it remained unchanged for other steroids. Before treatment, ACTH stimulus induced a significant response in all parameters; after the treatment, it prompted a greater response in Δ5-and Δ4-androgens, progesterone and 17-OH progesterone, while Cortisol responded less in both younger and older normal-weight women. The endometrial thickness did not show significant modifications in any of the groups of postmenopausal women during the 6 months of treatment. Treatment with DHEA was associated with a progressive improvement of the Kupperman score in all groups, with major effects on the vasomotor symptoms in the early postmenopausal women.In conclusion, the present findings confirm that DHEA supplementation produces physiological and supraphysiological modifications in steroid milieu and adrenal function. The beneficial effects of DHEA on the quality of life and in reverting the aging process may be related to changes in the release of adrenal products and/or peripheral steroids, with an increase in anxiolytic (allopregnanolone), anabolic (androstenedione, testosterone, dihydrotestosterone) and estrogenic (estrone, estradiol) molecules, a beneficial decrease in Cortisol and increase in pituitary β-endorphin production.